Tumor Evolution in Space: The Effects of Competition Colonization Tradeoffs on Tumor Invasion Dynamics

Abstract

We apply competition colonization tradeoff models to tumor growth and invasion dynamics to explore the hypothesis that varying selection forces will result in predictable phenotypic differences in cells at the tumor invasive front compared to those in the core. Spatially, ecologically, and evolutionarily explicit partial differential equation models of tumor growth confirm that spatial invasion produces selection pressure for motile phenotypes. The effects of the invasive phenotype on normal adjacent tissue determine the patterns of growth and phenotype distribution. If tumor cells do not destroy their environment, colonizer and competitive phenotypes coexist with the former localized at the invasion front and the latter, to the tumor interior. If tumors cells do destroy their environment, then cell motility is strongly selected resulting in accelerated invasion speed with time. Our results suggest that the widely observed genetic heterogeneity within cancers may not be the stochastic effect of random mutations. Rather, it may be the consequence of predictable variations in environmental selection forces and corresponding phenotypic adaptations.

Differential Distribution of microRNAs in Breast Cancer Grouped by Clinicopathological Subtypes

“…In addition, it has become gradually accepted that applying competition colonization tradeoff models to tumor growth and invasion dynamics can be useful for exploring the hypothesis that varying selection forces will result in predictable phenotypic differences in cells at the tumor invasive front compared to those in the core (Orlando et al, 2013).…”

Life history trade-offs in cancer evolution

“…Tumors are mosaics of different microenvironments. Regions of low but stable resource availability (e.g., hypoxia) promote strong competitor neoplastic cells (tumor interior), while regions with high or fluctuating resource availabilities allow for the coexistence of the cells with traits for inefficient but rapid proliferation (e.g., edge of the tumor) 36 . Life history phenotypes in cancers should in general reflect proximity to blood flow 37 , the availability of resources, fluctuations in these availabilities, and extrinsic sources of mortality such as immune predation and chemotherapy.…”

“…These temporal variations in resources should select for cells that proliferate quickly, over-exploit their environments and have higher rates of dispersal 19, 20 . The coexistence of both stable and fluctuating microenvironments should both select for and permit the coexistence of both fast and slow life history phenotypes within the same tumor 36 . Tradeoffs between quick colonization (i.e., rapid division and migration into areas of unutilized resources) and effective competition (i.e., investment in survival) have been associated with coexistence and the evolution of slow and fast life histories in some ciliate protists 40 .…”

“…It has been suggested that life history traits contribute to the phenotypic plasticity among social insects (i.e., developmental diet of female honeybee larvae determines worker vs. queen) 73 . Under such an adaptation, the diversity of traits seen in the population emerges from a single flexible “species” rather than the coexistence of genetically distinct specialist species or clones 36 . Cancer stem cells may provide such a dynamic adaptation where their generalist strategy creates morphological diversity but not the genetic heterogeneity that would be found from the coexistence of tumor cell lineages with specialist traits for either a fast or slow life history strategies.…”

Zebrafish Xenograft: An Evolutionary Experiment in Tumour Biology

“…Presumably, the same principle can drive the structure and function of the TME, but little is known about how sub-clonal cell populations contribute to the basic structure of the ECM. While we have begun to map spatial heterogeneity to increase our understanding of how these cells interact with each other and their environment, this has largely been focused on the organization of nontumour cells [39] or subpopulations of tumour cells [11]. Currently, we study the TME largely through the lens of angiogenesis, immune modulation or cell morphology, with the latter having not been revisited since the end of the twentieth century.…”